Conspecific Presence Promotes Social Buffering, Restores Social Reward, and Enhances Spatial Navigation in a Ketamine‐Induced Model of Schizophrenia in Mice

Despite extensive research on the effects of enriched environments in mouse models of psychiatric disorders, the role of social context remains poorly explored. Therefore, we assessed the impact of a conspecific during the evaluation of negative and cognitive symptoms in a mouse model of schizophrenia (SCZ). Male C57BL/6J mice received daily injections of ketamine (25 mg/kg) or vehicle. Behavioral testing was conducted with mice either alone or in dyads of varying familiarity. Anxiety-like behavior and habituation were assessed using the 3D maze test (3DM). Social reward was measured with a social conditioned place preference test. Finally, episodic memory was evaluated using an object recognition memory test (ORMT). Ketamine induced anxiogenic-like behavior and impaired habituation, social reward, and spatial memory. In contrast, the presence of a conspecific induced anxiolytic-like behavior, accelerated habituation, and restored social reward. Additionally, greater dyad familiarity led to better performance in the 3DM. Conversely, the presence of a conspecific did not rescue cognitive deficits in the ORMT; however, spatial navigation in the 3DM was improved. These results support that the presence of a conspecific induces social buffering and promotes prosocial behavior. Therefore, this highlights a therapeutic effect modulated by social context and introduces a new model to evaluate social cognition in a mouse model of SCZ.